Emerging evidence indicates that maternal medical risk during pregnancy, such as gestational diabetes mellitus (GDM), preeclampsia, and obesity, predisposes the offspring to suboptimal development. However, the underlying biological/epigenetic mechanism in utero is still unknown. The current pilot study (N ¼ 50) compared the levels of global methylation in the placenta and umbilical cord blood among women with and without each risk condition (GDM, preeclampsia, and obesity) and explored whether the levels of global methylation were associated with fetal/infant growth. Results show that global methylation levels in the placenta were lower in patients with gestational diabetes (P ¼ .003) and preeclampsia (P ¼ .05) but higher with obesity (P ¼ .01). Suggestive negative associations were found between global methylation level in the placenta and infant body length and head circumference. While preliminary, it is possible that the placenta tissue, but not umbilical cord blood, may be epigenetically programmed by maternal GDM, preeclampsia, and obesity to carry out its own specific functions that influence fetal growth.

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Background Little is known about the impact of prenatal maternal stress (PNMS) on the developmental trajectory of temperament and few studies have been able to incorporate a natural disaster as a quasi-experimental stressor. The current study investigated PNMS related to Superstorm Sandy (‘Sandy’), a hurricane that struck the New York metropolitan area in October 2012, in terms of objective exposure during pregnancy, subjective stress reaction as assessed by maternal symptoms of post-traumatic stress, and their impact on the developmental changes in temperament during early childhood. Method A subsample of 318 mother-child dyads was drawn from the Stress in Pregnancy Study. Temperament was measured at 6, 12, 18, and 24 months of age. Results Objective exposure was associated with greater High-Intensity Pleasure, Approach, Perceptual Sensitivity and Fearfulness, but lower Cuddliness and Duration of Orientation at 6 months. Objective exposure and its interaction with subjective stress reaction predicted developmental changes in temperament. In particular, objective exposure was linked to greater increases in Activity Level but decreases in High-Intensity Pleasure, Approach, and Fearfulness. The combination of objective exposure and subjective stress reaction was also associated with greater increases in Activity Level. Limitations Temperament was measured solely via maternal report. Trimester-specific effects of Sandy on temperament were not examined. Conclusion This is the first study to examine the effects of prenatal maternal exposure to a natural disaster on trajectories of early childhood temperament. Findings suggest that both objective stress exposure and subjective stress reaction in-utero predict developmental trajectories of temperament in early childhood.

The study examined the effects of in-utero exposure to maternal depression and Superstorm Sandy, a hurricane that hit metropolitan New York in 2012, on infant temperament at 6 months. Temperament was assessed using the Infant Behavior Questionnaire-Revised. Maternal depression was measured by the Edinburgh Postnatal Depression Scale. The main effects and the interaction of maternal depression and Sandy exposure on infant temperament were examined using Multivariable General Linear Model. Results show that prenatal maternal depression was associated with lower emotion-regulation and greater distress. Stratification and interaction analyses suggested that the adverse effects of prenatal maternal depression on problematic temperament were amplified by in-utero Sandy exposure. The study underscores the importance of providing prenatal screening and treatment for maternal depression during pregnancy, while simultaneously identifying high-risk families who may have suffered from disaster-related traumas in order to provide necessary services. As the frequency of natural disasters may increase owing to climate change, it is important to understand the consequences of in-utero stress on child development and to formulate plans for early identification.

to understand the extent to which an adverse environment in utero can alter fetal growth and development, with potential lifelong impacts on health and disease, based on the theoretical framework of the 'Developmental Origins of Health and Diseases (DoHaD) Hypothesis'. [1][2][3][4][5][6] Growing evidence [7][8][9] suggests that not only the genome but also the epigenome, the heritable, quasi-stable yet dynamic control of gene expression, can be modulated by the environment, and plays a vital role in defining health and disease in growing offspring. [10][11][12] Preclinical studies demonstrated that antenatal stress leads to dysregulated neurobehavioural functioning and problems with development, providing a solid platform for hypothesis testing in human studies. Human studies have also demonstrated that antenatal exposure to broadly defined stress (i.e. stressful life events and psychological problems) is linked to long-term neurobehavioural problems in offspring, 13,14 such as autism, 15,16 schizophrenia [17][18][19][20] and attention deficit/hyperactivity disorder, [21][22][23] as well as growth-related suboptimal reproductive outcomes such as intra-uterine growth restriction (IUGR) [24][25][26] and obesity, [27][28][29] through epigenetic mechanisms.Human studies remain hampered by methodological restrictions, including: (i) the inability to randomize pregnant women in varying stressful condition and to systematically control for the level and timing of any exposure; (ii) stressful c A graduate/professional degree includes higher level postgraduate degrees (Master's, MD, JD, PhD etc).

Purpose Preeclampsia is known to be a leading cause of mortality and morbidity among mothers and their infants. Approximately 3–8% of all pregnancies in the US are complicated by preeclampsia and another 5–7% by hypertensive symptoms. However, less is known about its long-term influence on infant neurobehavioral development. The current review attempts to demonstrate new evidence for imprinting gene dysregulation caused by hypertension, which may explain the link between maternal preeclampsia and neurocognitive dysregulation in offspring. Method Pub Med and Web of Science databases were searched using the terms “preeclampsia,” “gestational hypertension,” “imprinting genes,” “imprinting dysregulation,” and “epigenetic modification,” in order to review the evidence demonstrating associations between preeclampsia and suboptimal child neurodevelopment, and suggest dysregulation of placental genomic imprinting as a potential underlying mechanism. Results The high mortality and morbidity among mothers and fetuses due to preeclampsia is well known, but there is little research on the long-term biological consequences of preeclampsia and resulting hypoxia on the fetal/child neurodevelopment. In the past decade, accumulating evidence from studies that transcend disciplinary boundaries have begun to show that imprinted genes expressed in the placenta might hold clues for a link between preeclampsia and impaired cognitive neurodevelopment. A sudden onset of maternal hypertension detected by the placenta may result in misguided biological programming of the fetus via changes in the epigenome, resulting in suboptimal infant development. Conclusion Furthering our understanding of the molecular and cellular mechanisms through which neurodevelopmental trajectories of the fetus/infant are affected by preeclampsia and hypertension will represent an important first step toward preventing adverse neurodevelopment in infants.

ObjectiveWe sought to determine histologic and gene expression features of clinical improvement in early diffuse cutaneous systemic sclerosis (dcSSc; scleroderma).MethodsFifty-eight forearm biopsies were evaluated from 26 individuals with dcSSc in two clinical trials. Histologic/immunophenotypic assessments of global severity, alpha-smooth muscle actin (aSMA), CD34, collagen, inflammatory infiltrate, follicles and thickness were compared with gene expression and clinical data. Support vector machine learning was performed using scleroderma gene expression subset (normal-like, fibroproliferative, inflammatory) as classifiers and histology scores as inputs. Comparison of w-vector mean absolute weights was used to identify histologic features most predictive of gene expression subset. We then tested for differential gene expression according to histologic severity and compared those with clinical improvement (according to the Combined Response Index in Systemic Sclerosis).ResultsaSMA was highest and CD34 lowest in samples with highest local Modified Rodnan Skin Score. CD34 and aSMA changed significantly from baseline to 52 weeks in clinical improvers. CD34 and aSMA were the strongest predictors of gene expression subset, with highest CD34 staining in the normal-like subset (p<0.001) and highest aSMA staining in the inflammatory subset (p=0.016). Analysis of gene expression according to CD34 and aSMA binarised scores identified a 47-gene fibroblast polarisation signature that decreases over time only in improvers (vs non-improvers). Pathway analysis of these genes identified gene expression signatures of inflammatory fibroblasts.ConclusionCD34 and aSMA stains describe distinct fibroblast polarisation states, are associated with gene expression subsets and clinical assessments, and may be useful biomarkers of clinical severity and improvement in dcSSc.

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